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Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes.

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journal contribution
posted on 01.12.2021, 09:45 authored by Naser Ansari-Pour, Yonglan Zheng, Toshio F Yoshimatsu, Ayodele Sanni, Mustapha Ajani, Jean-Baptiste Reynier, Avraam Tapinos, Jason J Pitt, Stefan Dentro, Anna Woodard, Padma Sheila Rajagopal, Dominic Fitzgerald, Andreas J Gruber, Abayomi Odetunde, Abiodun Popoola, Adeyinka G Falusi, Chinedum Peace Babalola, Temidayo Ogundiran, Nasiru Ibrahim, Jordi Barretina, Peter Van Loo, Mengjie Chen, Kevin P White, Oladosu Ojengbede, John Obafunwa, Dezheng Huo, David C Wedge, Olufunmilayo I Olopade
Black women across the African diaspora experience more aggressive breast cancer with higher mortality rates than white women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast cancers, with RNA-seq in a subset, from women in Nigeria in comparison with The Cancer Genome Atlas (n = 76) reveal a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations with a 10.5-year younger age at diagnosis. We also find non-coding mutations in bona fide drivers (ZNF217 and SYPL1) and a previously unreported INDEL signature strongly associated with African ancestry proportion, underscoring the need to expand inclusion of diverse populations in biomedical research. Finally, we demonstrate that characterizing tumors for homologous recombination deficiency has significant clinical relevance in stratifying patients for potentially life-saving therapies.

Funding

Crick (Grant ID: 10202, Grant title: Van Loo FC001202)

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